tbuckley/cabot-search huggingface dataset:
Abstract 13028: Associations Between White Matter Microstructure, Resting and Peak Exercise Oxygen Saturations, and Cognitive Function in Adolescents and Adults With a Fontan Circulation; A Diffusion Brain MRI Study
Authors: Charlotte E Verrall, Jian Chen, Chun-Hung Yeh, Derek Tran, Karina Laohachai, Mark T MacKay, Yves d'Udekem, David S Winlaw, Ajay J Iyengar, Julian Ayer, Thomas L Gentles, Joseph Yang, Rachael Cordina
Journal: Circulation (2022)

Introduction: Adolescents and adults with a Fontan circulation demonstrate broad cognitive dysfunction. Neurological alterations and risk factors associated with worse outcomes are poorly characterized. Persisting hypoxemia and reduced exercise tolerance are also common and are associated with long-term morbidity and mortality. This study investigated white matter (WM) microstructure in adolescents and adults with a Fontan circulation and associations with CPET data and cognitive functioning. Methods: Ninety-two participants with a Fontan circulation (aged 13-49 years) underwent diffusion brain MRI. Diffusion tensor imaging MRI metrics were computed for 34 WM tracts of interest; Lower FA and higher MD and RD typically infers WM axonal injury and/or demyelination. Resting SaO 2, peak exercise SaO 2 , and % predicted peak VO 2 (%pred VO 2 ) were measured during CPET. Processing speed and executive function were assessed using Cogstate. Results: Mean resting and peak SaO 2 were 93.1% (± 3.81) and 90.1% (± 4.71) respectively and mean %pred VO 2 was 62.7% (± 18.5); all were significantly lower for participants with a patent fenestration compared to those without (p &lt; 0.05). Mean processing speed and executive function z-scores were -0.72 (± 1.44) and -0.43 (± 1.09), respectively. Significant associations were identified between i) resting SaO 2 and the left corticospinal tract (CST) and bilateral superior longitudinal fasciculus I (SLF-I) ii) peak SaO 2 and bilateral CST, frontopontine tract, and SLF-I and -II, and the right SLF-III, and iii) %pred VO 2 and the right cingulum and left uncinate fasciculus (p &lt; 0.05), whereby lower resting and peak SaO 2 and %pred VO 2 were associated with lower FA and/or higher MD and RD. Paradoxical associations were identified between processing speed and executive function and WM tract metrics (p &lt; 0.05). Conclusion: Persisting hypoxemia and exercise intolerance may have long-term detrimental impact on WM microstructure in people with a Fontan circulation. Paradoxical associations between cognitive functioning and DTI-based metrics could be suggestive of compensatory WM remodeling. Longitudinal investigations are required to investigate the mechanisms and trajectory of altered WM microstructure in this cohort.
Abstract 14797: Single Cell Multi-Modal Analyses Reveal Epigenomic and Transcriptomic Basis Underlying Cardiac Defects in Maternal Diabetes
Authors: Tomohiro Nishino, Sanjeev Ranade, Pelonero Angelo, Benjamin J van Soldt, Lin Ye, Michael Alexanian, Frances Koback, Yu Huang, Nandhini Sadagopan, Arun Padmanabhan, Reuben Thomas, Joke van Bemmel, Casey Gifford, Mauro Costa, Deepak Srivastava
Journal: Circulation (2022)

Introduction: Birth defects can be caused by combinations of genetic and environmental influences. Large-scale DNA sequencing efforts reveal genetic influences, yet the environmental contributions have been mainly limited to association studies with little mechanistic insight. Hyperglycemia in pre-gestational diabetic (PGDM) mothers are among the most frequent environmental contributors to congenital defects, such as congenital heart defects and craniofacial anomalies. However, the cell types involved and underlying mechanisms by which PGDM affects these regions are unknown. Methods and Results: To determine how PGDM affects the epigenomic and transcriptomic state within individual cells during cardio-pharyngeal development, we utilized multi-modal single cell analyses with streptozotocin-induced mouse PGDM model. Analysis of E10.5 embryos showed that PGDM specifically affects the epigenomic state of two small subsets of cardiac and craniofacial progenitors. In PGDM derived embryos, a newly recognized subpopulation of anterior heart field progenitors expressing Alx3 acquires a more posterior-like identity in response to PGDM, based on gene expression and chromatin status. Similarly, a sub-population of neural crest-derived cells in the second pharyngeal arch, which contributes to craniofacial structures, also displayed patterning abnormalities. Analyses of differentially accessible chromatin regions revealed disrupted patterning was due to increased intrinsic retinoic acid signaling in affected cell types in PGDM. Conclusions: We showed the selective epigenomic vulnerability of a small subset of cells that help explain cardiac and craniofacial defects observed in PGDM despite all embryonic cells experiencing similar environmental exposure. We also showed that the selectivity was partly driven by a previously unrecognized dysregulation of retinoic acid signaling in PGDM. Discovery of the consequences of environmental factors on embryonic development using multi-modal single cell genomics will lead to potential gene-environment combinations that contribute to the complex and multifactorial diseases and preventive approaches to protect vulnerable cells.
Abstract 14907: Association Between Adverse Pregnancy Outcomes and N-Terminal Pro-Brain Natriuretic Peptide 2-7 Years After Delivery: Numom2b Heart Health Study
Authors: Priya M Freaney, Xiaoning Huang, Lucia C Petito, William A Grobman, Janet Catov, Alisse Hauspurg, C. Noel Bairey Merz, Natalie A Bello, Judith Chung, Abbi D Lane-Cordova, David M Haas, Lisa D Levine, Rebecca B McNeil, Eliza C Miller, George Saade, Lauren Theilen, Lynn M Yee, Philip Greenland, Sadiya S Khan
Journal: Circulation (2022)

Introduction: Adverse pregnancy outcomes (APOs), including gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and small-for-gestational age (SGA), have been associated with increased risk of heart failure (HF), but mechanisms are poorly understood. We sought to examine the association between a history of APO and N-terminal pro-brain natriuretic peptide (NT-proBNP), a HF biomarker, after delivery. Methods: We included individuals from the NuMoM2b Heart Health Study who were recruited during their first pregnancy and followed longitudinally. We excluded individuals who had pre-pregnancy hypertension or diabetes. APOs were centrally adjudicated based on medical records. NT-proBNP was assessed at follow-up visit after delivery. We examined the association between a history of APO and elevated NT-proBNP (≥125 pg/mL) with logistic regression. We log-transformed NT-proBNP and also examined the association between history of APO and NT-proBNP with linear regression. Models were adjusted for demographic and cardiovascular risk factors at the time of NT-proBNP. Results: Of 4172 individuals, mean (SD) age was 30.7(5.6) years at 3 years follow-up after delivery and 170 (4%) had a history of GDM, 597 (14%) HDP, 321 (8%) had PTB, and 170 (4%) had SGA. Among the study population, 256 (6%) had elevated NT-proBNP. Individuals with GDM had a lower risk of elevated NT-proBNP levels (adjusted odds ratio 0.59 [95% confidence interval 0.38, 0.92]); while a history of HDP, PTB, or SGA was not associated with elevated NT-proBNP ( TABLE ). When NT-proBNP was examined as a continuous variable, a history of GDM (-0.20 [-0.35, -0.06] pg/mL) or HDP (-0.09 [-0.15, -0.02]) was associated with lower log-transformed NT-proBNP levels in adjusted models. Conclusions: In this cohort study, APOs were not associated with elevations in NT-proBNP, but GDM and HDP were paradoxically associated with lower NT-proBNP levels at 3 years post-delivery.
Abstract 14760: Troponin Leak in Sepsis: Does it Correlate With Hemodynamics?
Authors: Dimitrios Varrias, Sanjana Nagraj, Majd Al Deen Alhuarrat, Suraj Krishnan, Anika Sasidharan, Sindhu Vikash, Amrin Kharawala, ISRAEL SAFIRIYU, Luis Cerna, Perminder Gulani, Miguel Alvarez, Robert Faillace
Journal: Circulation (2022)

Introduction: Although several studies have demonstrated that elevated troponin predicts mortality in septic patients, data concerning the independent risk factors predisposing to higher chance of troponin leak are conflicting. Hypothesis: In this study we aim to identify predictors of troponinemia and lactatemia in the setting of sepsis and more specifically to clarify how hemodynamics affect these biomarkers. Methods: This is a retrospective cohort study on patients admitted to the intensive care units with severe sepsis. A total of 354 patients were included. Elevated admission troponin-T and lactate were defined as ≥0.01ng/mL and 2.5mmol/L respectively. Modified shock index defined as heart rate/mean arterial blood pressure (MSI) was used as a surrogate of hemodynamic instability. Linear regression models where generated to examine multi variate associations and Cox regression models were used for mortality outcomes. Analysis was done using STATA I/C 16.1. Results: The only independent predictor of elevated troponin in the setting of septic shock was pre-existing coronary artery disease (Coef.= 6 [1.9 - 10] p = 0.001). Troponin was not associated with mean arterial pressure (MAP) nor Modified Shock Index (Heart rate/MAP). On the other hand, elevation of lactate was significantly associated with Modified Shock index (Coef.=1.7 [CI 0.4 - 3] p= 0.001) and history of Diabetes (Coef.=1.2[0.04-2.3] p= 0.04). In a Cox regression modeling assessing for predictors of mortality in septic shock, lactate levels were strongly associated with death (OR= 1.17 [1.12-1.2] p= 0.0001) followed by male sex (OR= 1.8 [1.02-3] p=0.04) and Modified Shock Index (OR=1.5 [1.23-3.2] p=0.03) but troponin leak failed to show any correlation with mortality. Conclusions: Troponin leak is associated only with pre-existing CAD, not associated with hemodynamics and does not predict mortality.
Abstract 13575: Utilizing Electronic Health Record Alerts to Increase Prescription of Lipid Lowering Therapies in Patients Admitted With Acute Coronary Syndromes
Authors: Kent Brummel, Christopher Zimmerman, Michael Madigan, Adam Stein, Eric Brandt, Devraj Sukul, Sarah Adie
Journal: Circulation (2022)

Introduction:Patients who present to the hospital with acute coronary syndromes (ACS) often have poor control of cardiac risk factors. Multiple studies have demonstrated that lipid lowering therapy is not appropriately initiated or intensified in these patients.Hypothesis:We hypothesized that an interruptive alert delivered via the electronic medical record would increase the initiation and intensification of lipid lowering therapies.MethodsUsing Epic EHR (Epic Systems, Verona, WI), an interruptive alert was designed to trigger upon opening the patient’s chart when the patients were admitted with an ICD code that indicated an ACS (i.e., STEMI, NSTEMI, or Unstable Angina). The alert included an order set to obtain a cholesterol panel or if a cholesterol panel had already been collected it would be displayed and suggest modifications to the patient’s current medication regimen. These alterations included statin intensification or the addition of ezetimibe.ResultsBetween September 1, 2021 and May 30, 2022 172 unique patients were identified. The mean age was 64.8 ±13.8 years, 64.5% were male, 74% were white, and 12% were black. The identified patients had multiple comorbidities including cerebrovascular disease (23%), heart failure (47%), peripheral vascular disease (30%), and being a current or former smoker (53%). The triggered order set had a direct effect on 42 (24%) patients, with 10 initiating ezetimibe and 32 having their statins intensified. The most common indicated reason for overriding the alert (n=99) was not meeting criteria. Of these 99 patients, 4 were ultimately started on ezetimibe, 57 had their statin intensified, and 23 were appropriately excluded (including patients with type II myocardial infarctions who were not the target of this intervention). Of note, 15 patients should have received intensified therapy but had their alert over ridden.ConclusionsThis targeted alert led to direct intensification of lipid lowering therapy in 24% of ACS patients with an additional 35% of patients identified by the alert also having therapeutic intensification. This alert will remain in place to allow for further assessment of its effects and can be easily translated to other clinical systems.
Abstract 14804: Are Mobile Cardiac Outpatient Monitors Reliable to Monitor Qtc in Comparison to 12 Lead ECG
Authors: Adnan Ahmed, Jalaj Garg, Rishi Charate, Naga Venkata K Pothineni, Rajesh Kabra, Rakesh Gopinathannair, Dhanunjaya Lakkireddy
Journal: Circulation (2022)

Introduction: Use of mobile cardiac outpatient monitor (MCOT) increased during the COVID-19 pandemic as a substitute for telemetry and monitoring of arrythmias during loading of antiarrhythmic drugs (AAD). However, data comparing difference of QTc interval between a MCOT, and 12 lead ECG is scare. Hypothesis: To assess the accuracy of mobile cardiac outpatient monitor in comparison to 12 lead ECG for QTc monitoring Methods: We prospectively evaluated 24 patients at our institution who received IV sotalol as single day loading dose for initiation of oral sotalol therapy for atrial fibrillation/atrial flutter (AF/AFL). All patients were discharged 6 hours after the IV loading dose with a MCOT for 3 days. All patients had a 12 lead ECG within 12-18 hours of the baseline line MCOT transmission. Variation in heart rate and QTc was assessed. Results: A total of 24 patients were included in the study. The mean age was 65 + 7.3 years, 80% of patients were men. The mean difference between the QTc interval measured on 12 lead ECG and MCOT was 5.1 + 6 milliseconds [450 + 33 (EKG) - 445 + 39 (MCOT)], p=0.92. The mean heart rate difference between the two modalities was also not significant, p=0.726 [ 70.4 + 19 (EKG) -72 + 11.8 (MCOT), ΔHR=1.6 + 7.2 beats per minute]. Conclusions: MCOT can be considered as a reliable alternate to 12 lead ECG for monitoring of QTc in patients receiving AAD.
Abstract 13417: Deletion of the Asialyloglycoprotein Receptor-1 Causes Athero-Protective Effects <i>in vitro</i> and <i>in vivo</i>
Authors: Benjamin J Pullen, Achini K Vidanapathirana, Lauren Sandeman, Arun Everest-Dass, Daniel Kolarich, Joanne T Tan, Peter Psaltis, Stephen Nicholls, Nicolle H Packer, Christina A Bursill
Journal: Circulation (2022)

Introduction: The asialoglycoprotein receptor-1 (ASGR-1) is known to be a hepatic receptor that clears desialylated glycoproteins from the circulation. A loss-of-function mutation in ASGR-1 was reported to associate with a 34% reduction in coronary artery disease (CAD) risk, suggesting a role for ASGR-1 in CAD. Hypothesis: ASGR-1 is an important player in atherosclerosis and deletion of ASGR-1 will reduce atherosclerotic plaque via athero-protective mechanisms in macrophages. Methods and Results: Using immunofluorescence, we detected ASGR-1 in aortic sinus plaques from apolipoprotein (Apo)e-/- mice fed a high cholesterol diet (HCD)-fed apolipoprotein (Apo)e-/- mice. Bone marrow-derived macrophages (BMDMs) from Asgr1-/- mice elicited greater cholesterol efflux (39%, P&lt;0.05) and decreased oxLDL uptake (15%, P&lt;0.05), compared to wildtype BMDMs. Plasma from Asgr-1 -/- mice had lower total cholesterol (25%, P&lt;0.05) and LDL cholesterol (36%, P&lt;0.05) concentrations than wildtype control mice. Apoe -/- x Asgr-1 -/+ mice fed HCD for 8 weeks developed less plaque in the aortic sinus (32.75%, P&lt;0.001) than Apoe -/- controls, and had fewer circulating neutrophils (38%, P&lt;0.05). In the tandem stenosis model of unstable plaque, Apoe -/- x Asgr-1 -/- mice also developed smaller plaques in their carotid arteries (49%, P&lt;0.05), than Apoe -/- controls. Furthermore, ASGR-1 was measured in peripheral blood mononuclear cells (PBMCs) isolated from patient samples (n=10-12/group). ASGR-1 protein levels were higher in PBMCs from patients with coronary plaque (61%, P&lt;0.05), than those without plaque, as determined from coronary angiograms. Conclusions: ASGR-1 plays an important role in atherosclerosis. Deletion of ASGR-1 causes athero-protective effects in macrophages in vitro and reduced plaque burden in vivo . Elevated ASGR-1 levels in PBMCs from clinical blood samples was also associated with the presence of coronary plaque. These studies have significant implications for the potential of ASGR-1 as a therapeutic target for the prevention of atherosclerosis.
Abstract 13019: LV Thrombus With Embolic Phenomena: Identifying the Culprit
Authors: Sara Samaan, Melissa Moey, Wayne Kreeger
Journal: Circulation (2022)

Background: Left ventricular (LV) thrombus occurs with prior myocardial infarction (MI), particularly anterior ST-elevation MI (STEMI), dilated cardiomyopathy, and prothrombotic conditions. Case: A 38-year-old female with poorly controlled type 2 diabetes mellitus presented with leg pain and dyspnea. Her left lower extremity was cold and mottled, with absent pulses in both legs. EKG revealed lateral STEMI. Emergent coronary angiogram revealed 85% proximal left circumflex stenosis and 100% stenosis of the proximal first obtuse marginal branch (not amenable to intervention due to small vessel caliber). The patient then underwent bilateral iliofemoral and popliteal embolectomy. Transthoracic echocardiogram revealed ejection fraction (EF) of 40% and a 1 x 1 cm thrombus attached to the posteromedial papillary muscle; heparin was started. The patient later developed right-sided weakness; brain MRI revealed multiple acute-subacute infarcts in the left cerebral hemisphere. Transesophageal echocardiogram was negative for patent foramen ovale or shunt. Decision-making: LV thrombus with embolic phenomena raised suspicion for underlying thrombophilia. The patient was started on warfarin and clopidogrel, with outpatient follow-up for hypercoagulability workup, which was negative. Cardiac MRI later revealed resolution of LV thrombus, and oral anticoagulation was discontinued after 3 months, and switched to aspirin. Conclusion: LV thrombus is far more common after anterior STEMI as it affects a larger area of myocardium, but it can also occur with lateral STEMI. Hypercoagulability state should be considered on the differential of LV thrombus in the setting of lateral STEMI. If hypercoagulability workup is negative, aggressive risk factor modification for coronary disease should be pursued.
Abstract 13940: Intra-Operative Findings With Massive Device-Related Thrombus After Percutaneous LAA Closure: Mechanistic Insights
Authors: Kashif Malik, Rong Bai, Damir Vukomanovic, Alicia Taase, Eleanor Kitchell, Rinku Skaria, Roderick Tung, Kenith Fang, Michael Zawaneh
Journal: Circulation (2022)

Background: Device related thrombus (DRT) has an observed incidence of ~4% after left atrial appendage closure (LAAC), of which the mechanism remains incompletely understood. Objective: To present and examine the intraoperative findings of 2 cases of massive DRT occurring late post LAAC device implantation and propose potential mechanisms for these rare complications. Methods: N/A Results: Patient 1 was a 75-year-old female with paroxysmal AF and CHA2DS2-VASc Score of 5 with Watchman implanted two years prior to presentation. She had completed 45 days of warfarin and ASA after implantation. She underwent elective open heart surgery for severe mitral valve regurgitation and moderate to severe aortic valve regurgitation. Large DRT (2x2cm) was diagnosed intraoperatively, which was treated with left atrial appendage and device resection. Patient 2 was a 75-year-old female with permanent AF and CHA2DS2-VASc Score of 5, who was referred for routine postimplant surveillance TEE. She had also completed 45 days of warfarin and ASA after implantation. A large DRT measuring 2 x 2 cm was noted. The patient was treated with warfarin and subsequently dabigatran with improvement in the size of thrombus on TEE. However, a gastrointestinal bleed led to the cessation of anticoagulation. Subsequent TEE demonstrated enlargement of massive DRT (3x2 cm). She was referred to cardiac surgery for thrombectomy and resection of the Watchman device and LAA. Discussion/Conclusion: In both cases, the intraoperative findings demonstrate well-seated LAAC without gross findings of malapposition or peri-device leaks. The central screw was visible without evidence of endothelialization in both cases (Figure 1). An exposed central screw could be a possible nidus for thrombus formation.
Abstract 13506: Three-Dimensional Transoesophageal Echocardiography Characterization of Left Atrial Appendage Dimensions in Patients With Spontaneous Cardioversion of Atrial Fibrillation
Authors: Laurie Soulat-Dufour, Theo SIMON, Sylvie Lang, Stephane EDERHY, Saroumadi ADAVANE, Marion Chauvet-Droit, Pascal Nhan, Elodie Capderou, Iris Kamami, Camille Arnaud, Pierre-Antoine Lebos, Pauline Issaurat, Franck Boccara, Ariel A COHEN
Journal: Circulation (2022)

Introduction: Few studies have described the clinical profile and natural history of patients with spontaneous cardioversion (SpCV) in atrial fibrillation (AF). Hypothesis: We hypothesized that patients with SpCV have a distinct morphological pattern in AF. Methods: We prospectively evaluated 262 patients hospitalized for AF using two-dimensional (2D) transthoracic (TTE) and three-dimensional (3D) transoesophageal echocardiography (TEE). 3D parameters were off-line analysed using Tomtec software (4D Cardio-View, Philips). Patients were divided into two groups according to the cardiac rhythm within 24 hours after admission: spontaneous cardioversion (SpCV group, 59 patients) and non-spontaneous cardioversion (noSpCV group, 203 patients). Results: Mean age of the population was 66±12 years and 166 (63%) patients were male. SpCV group had in comparison with noSpCV group lower CRP levels (respectively 3.3(3-5.5) versus 4(3-10) mg/L, p=0.0394), lower BNP levels (151(67-200) versus 269(129-424) pg/mL, p&lt;0.001) and lower HBA1c levels (5.5(5.3-5.7) versus 5.9(5.6-6.3) %, p&lt;0.0001). Using 2D TTE, SpCV group had in comparison with noSpCV group lower indexed left atrial end-systolic volume, lower indexed right atrial end-systolic volume, lower E velocity, and higher left ventricle ejection fraction (Table 1). Based on 2D and 3D TEE, SpCv group had in comparison with noSpCV group higher LAA emptying flow velocity and higher LAA filling flow velocity, lower 3D end-systolic and end-diastolic LAA volumes (both non-indexed and indexed) and lower 3D LAA ostium in comparison with noSpCV group (Table 1). Conclusions: Although SpCv of AF is a frequent situation incompletely studied, clinical and echocardiographic characteristics could be described. Further investigations are needed to determine the impact of such abnormalities on the prognosis in the SpCV group.